Background:Studies have revealed the protective effect of DL-3-n-butylphthalide(NBP)against diseases associated with ischemic hypoxia.However,the role of NBP in animals with hypobaric hypoxia has not been elucidated.T...Background:Studies have revealed the protective effect of DL-3-n-butylphthalide(NBP)against diseases associated with ischemic hypoxia.However,the role of NBP in animals with hypobaric hypoxia has not been elucidated.This study investigated the effects of NBP on rodents with acute and chronic hypobaric hypoxia.Methods:Sprague-Dwaley rats and Kunming mice administered with NBP(0,60,120,and 240 mg/kg for rats and 0,90,180,and 360 mg/kg for mice)were placed in a hypobaric hypoxia chamber at 10,000 m and the survival percentages at 30 min were determined.Then,the time and distance to exhaustion of drug-treated rodents were evaluated during treadmill running and motor-driven wheel-track treadmill experiments,conducted at 5800 m for 3 days or 20 days,to evaluate changes in physical functions.The frequency of active escapes and duration of active escapes were also determined for rats in a shuttle-box experiment,conducted at 5800 m for 6 days or 27 days,to evaluate changes in learning and memory function.ATP levels were measured in the gastrocnemius muscle and malonaldehyde(MDA),superoxide dismutase(SOD),hydrogen peroxide(H_(2)O_(2)),glutathione peroxidase(GSH-Px),and lactate were detected in sera of rats,and routine blood tests were also performed.Results:Survival analysis at 10,000 m indicated NBP could improve hypoxia tolerance ability.The time and distance to exhaustion for mice(NBP,90 mg/kg)and time to exhaustion for rats(NBP,120 and 240 mg/kg)significantly increased under conditions of acute hypoxia compared with control group.NBP treatment also significantly increased the time to exhaustion for rats when exposed to chronic hypoxia.Moreover,240 mg/kg NBP significantly increased the frequency of active escapes under conditions of acute hypoxia.Furthermore,the levels of MDA and H_(2)O_(2) decreased but those of SOD and GSH-Px in the sera of rats increased under conditions of acute and chronic hypoxia.Additionally,ATP levels in the gastrocnemius muscle significantly increased,while lactate levels in sera significantly decreased.Conclusion:NBP improved physical and learning and memory functions in rodents exposed to acute or chronic hypobaric hypoxia by increasing their anti-oxidative capacity and energy supply.展开更多
The present study evaluated the effect of dl-3-n-butylphthalide(NBP) ,a novel brain protective agent, on brain edema in rats following focal ischemia. Edema was induced by occluding the right middle cerebral artery (M...The present study evaluated the effect of dl-3-n-butylphthalide(NBP) ,a novel brain protective agent, on brain edema in rats following focal ischemia. Edema was induced by occluding the right middle cerebral artery (MCAO).producing permanent focal ischemia in the right cerebral hemisphere,which developed ip-silateral brain edema reproducibly. Edema was assessed 24 h after MCA occlusion by determining the brain water content from wet and dry weight measurements,and the sodium,potassium concentrations with ion-selective electrodes. In this model,NBP at the dose of 80,160 and 240 mg/kg po 15 min after MCAO prevented from brain edema in a dose-dependent manner. A significant reduction of sodium content and an increase in potassium level were observed in all drug-treated groups. It showed that NBP strongly attenuated brain water entry,sodium accumulation and potassium loss. Nimodipine treatment(5mg/kg sc) also reduced brain edema (P<0. 05). The results suggest that a strong anti-edema activity of NBP may play an important role to contribute to the treatment of ischemic damage.展开更多
基金supported by grants from the National Science and Technology Major Project(2014ZX09J14102-05B and 2018ZX09J18109)。
文摘Background:Studies have revealed the protective effect of DL-3-n-butylphthalide(NBP)against diseases associated with ischemic hypoxia.However,the role of NBP in animals with hypobaric hypoxia has not been elucidated.This study investigated the effects of NBP on rodents with acute and chronic hypobaric hypoxia.Methods:Sprague-Dwaley rats and Kunming mice administered with NBP(0,60,120,and 240 mg/kg for rats and 0,90,180,and 360 mg/kg for mice)were placed in a hypobaric hypoxia chamber at 10,000 m and the survival percentages at 30 min were determined.Then,the time and distance to exhaustion of drug-treated rodents were evaluated during treadmill running and motor-driven wheel-track treadmill experiments,conducted at 5800 m for 3 days or 20 days,to evaluate changes in physical functions.The frequency of active escapes and duration of active escapes were also determined for rats in a shuttle-box experiment,conducted at 5800 m for 6 days or 27 days,to evaluate changes in learning and memory function.ATP levels were measured in the gastrocnemius muscle and malonaldehyde(MDA),superoxide dismutase(SOD),hydrogen peroxide(H_(2)O_(2)),glutathione peroxidase(GSH-Px),and lactate were detected in sera of rats,and routine blood tests were also performed.Results:Survival analysis at 10,000 m indicated NBP could improve hypoxia tolerance ability.The time and distance to exhaustion for mice(NBP,90 mg/kg)and time to exhaustion for rats(NBP,120 and 240 mg/kg)significantly increased under conditions of acute hypoxia compared with control group.NBP treatment also significantly increased the time to exhaustion for rats when exposed to chronic hypoxia.Moreover,240 mg/kg NBP significantly increased the frequency of active escapes under conditions of acute hypoxia.Furthermore,the levels of MDA and H_(2)O_(2) decreased but those of SOD and GSH-Px in the sera of rats increased under conditions of acute and chronic hypoxia.Additionally,ATP levels in the gastrocnemius muscle significantly increased,while lactate levels in sera significantly decreased.Conclusion:NBP improved physical and learning and memory functions in rodents exposed to acute or chronic hypobaric hypoxia by increasing their anti-oxidative capacity and energy supply.
文摘The present study evaluated the effect of dl-3-n-butylphthalide(NBP) ,a novel brain protective agent, on brain edema in rats following focal ischemia. Edema was induced by occluding the right middle cerebral artery (MCAO).producing permanent focal ischemia in the right cerebral hemisphere,which developed ip-silateral brain edema reproducibly. Edema was assessed 24 h after MCA occlusion by determining the brain water content from wet and dry weight measurements,and the sodium,potassium concentrations with ion-selective electrodes. In this model,NBP at the dose of 80,160 and 240 mg/kg po 15 min after MCAO prevented from brain edema in a dose-dependent manner. A significant reduction of sodium content and an increase in potassium level were observed in all drug-treated groups. It showed that NBP strongly attenuated brain water entry,sodium accumulation and potassium loss. Nimodipine treatment(5mg/kg sc) also reduced brain edema (P<0. 05). The results suggest that a strong anti-edema activity of NBP may play an important role to contribute to the treatment of ischemic damage.
基金supported by the National Natural Science Foundation of China(21002006,20452002)Special Program for Key Basic Research of the Ministry of Science and Technology,China(2004-973-36)~~
